ROBERTA BRAMBILLA, PH.D.

Research Assistant Professor, Department of Neurological Surgery

Modulation of the immune response in neurologic disease

Research Interest

The main focus of my research has been to understand the role of neuroinflammation in the pathophysiology of neurodegenerative disorders (e.g., spinal cord injury and multiple sclerosis), with a specific interest in the contribution of the astrocytes, a type of glial cell that represents the most abundant cell population in the nervous system.

I have been pursuing these investigations using a transgenic mouse model (GFAP-I {kappa}B{alpha} dominant negative mice) generated and characterized in collaboration with Dr. John Bethea. With this model we produced the first in vivo demonstration that selective inhibition of the astrocyte-mediated inflammatory response, by inactivating the transcription factor NF-{kappa}B specifically in this cell population, leads to significant functional recovery following spinal cord injury and experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS) [Brambilla et al., J. Exp. Med., 2005; Brambilla et al., J. Immunol., 2009]. In parallel to continuing to explore the role of astrocytes in the diseased nervous system in collaboration with Dr. Bethea, my laboratory is developing two specific lines of research in the area of neuroimmunology, which focus on:

1) Investigating the role of tumor necrosis factor, TNF, (both membrane-bound and soluble forms) in the processes of demyelination and remyelination. These studies would be relevant to understand the possible dichotomy of function of the two forms of TNF. More specifically, since the membrane-bound form of TNF has been associated with a possible role in remyelination, my interest is to evaluate whether this occurs, and by which mechanisms, in EAE. These studies are extremely relevant for two reasons: 1) they could lead to possible new therapies for MS (e.g., selective soluble-TNF inhibitors), which is the most diffuse neurodegenerative disorder in the United States; 2) they could shed light on the occurrence of demyelinating syndromes in patients treated with non-selective TNF inhibitors (e.g. Enbrel®) for autoimmune diseases such as rheumathoid arthritis and psoriasis.

2) Investigating the occurrence of neuropathic pain associated with multiple sclerosis. Although neuropathic pain is a condition developed by the majority of patients suffering from MS, this area of research is greatly under-represented. Indeed, immune-inflammatory cells infiltrating into the spinal cord during EAE or MS are capable of releasing pro-inflammatory mediators that can sustain the pain response. By understanding the mechanisms of multiple sclerosis-associated neuropathic pain, we could develop targeted treatments which could dramatically improve the quality of life of patients.